http://repub.eur.nl/res/aut/1325/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/13059/ 2002-04-01T00:00:00Z AIMS: We sought to compare the effect of intracoronary beta-radiation on the vessel dimensions in de novo lesions using three-dimensional intravascular ultrasound quantification after balloon angioplasty and stenting. METHODS AND RESULTS: Forty patients (44 vessels; 28 balloon angioplasty and 16 stenting) treated with catheter-based beta-radiation and 18 non-irradiated control patients (18 vessels; 10 balloon angioplasty and 8 stenting) were investigated by means of three-dimensional volumetric intravascular ultrasound analysis post-procedure and at 6-8 months follow-up. Total vessel (EEM) volume enlarged after both balloon angioplasty and stenting (+37 mm(3) vs +42 mm(3), P=ns), but vessel wall volume (plaque plus media) also increased similarly (+33 mm(3) vs +49 mm(3), P=ns) in the irradiated patients. Lumen volume remained unchanged in both groups (+3 mm(3) vs -7 mm(3), P=ns). In the stent-covered segments, neointima at follow-up was significantly smaller in the irradiated group than the control group (8 mm(3) vs 27 mm(3), P=0.001, respectively), but the total amount of tissue growth was similar in both groups (33 mm(3) vs 29 mm(3), P=ns). CONCLUSIONS: Intracoronary beta-radiation induces vessel enlargement after balloon angioplasty and/or stenting, accommodating tissue growth. Additional stenting may not play an important role in the prevention of constrictive remodelling in the setting of catheter-based intracoronary beta-radiotherapy. http://repub.eur.nl/res/pub/9837/ 2002-02-05T00:00:00Z BACKGROUND: Radioactive stents with an activity of 0.75 to 12 microCi have shown >40% edge restenosis due to neointimal hyperplasia and negative remodeling. This trial evaluated whether radioactive Cold Ends stents might resolve edge restenosis by preventing remodeling at the injured extremities. METHODS AND RESULTS: The 25-mm long (15-mm radioactive center and 5-mm nonradioactive ends) Cold Ends stents had an activity of 3 to 12 microCi at implantation. Forty-three stents were implanted in 43 patients with de novo native coronary artery disease. Two procedural, 1 subacute, and 1 late stent thrombosis occurred. A restenosis rate of 22% was observed with a shift of the restenosis, usually occurring at the stent edges of radioactive stents, into the Cold Ends stents. The most severe restenosis occurred at the transition zone from radioactive to nonradioactive segments, a region located in dose fall-off. CONCLUSION: Cold Ends stents did not resolve edge restenosis. http://repub.eur.nl/res/pub/9882/ 2002-01-01T00:00:00Z BACKGROUND: Because heterogeneous results have been reported, we assessed coronary flow velocity changes in individuals who underwent percutaneous transluminal coronary angioplasty (PTCA) and examined their impact on clinical outcome. METHODS AND RESULTS: As part of the Doppler Endpoints Balloon Angioplasty Trial Europe (DEBATE) II study, 379 patients underwent Doppler flow-guided angioplasty. All patients were evaluated according to their coronary flow velocity reserve (CFVR) results (> or =2.5 or < 2.5) at the end of the procedure. A CFVR < 2.5 after angioplasty was associated with an elevated baseline blood flow velocity in both the target artery and reference artery. CFVR before PTCA and CFVR in the reference artery were independent predictors of an optimal CFVR after balloon angioplasty (CFVR before PTCA: odds ratio [OR], 2.26; 95% confidence interval [CI], 1.57 to 3.24; CFVR in reference artery: OR, 1.90; 95% CI, 1.21 to 2.98; both P<0.001) and stent implantation (before PTCA: OR, 2.54; 95% CI, 1.47 to 4.36; reference artery: OR, 1.97; 95% CI, 1.07 to 3.87; both P<0.05). A low CFVR at the end of the procedure was an independent predictor of major adverse cardiac events (MACE) at 30 days (OR, 4.71; 95% CI, 1.14 to 25.92; P=0.034) and at 1 year (OR, 2.06; 95% CI, 1.16 to 3.66; P=0.014). After excluding MACE at 30 days, no difference in MACE at 1 year was observed between the patients with and without a CFVR < 2.5 at the end of the procedure. CONCLUSIONS: A low postprocedural CFVR was associated with a worse periprocedural outcome (which was related to microcirculatory disturbances), but there was no significant difference at late follow-up. http://repub.eur.nl/res/pub/23519/ 2001-09-19T00:00:00Z Angiographic restenosis occurs in up to 60% of cases after balloon angioplasty (BA). Restenosis after BA occurs due to elastic recoil of the artery, vascular remodeling with vessel shrinkage and neointimal hyperplasia. Neointimal hyperplasia develops by migration and proliferation of smooth muscle cells (SMCs) and myofibroblasts after balloon-induced trauma of the arterial wall and by deposition of an extracellular matrix by the SMCs. By preventing elastic recoil and negative remodeling stent implantation has resolved many of the problems created by balloon angioplasty. However, a new problem has been created - that of in-stent restenosis, which is caused by neointimal hyperplasia. This entity occurs in 9-30% of cases after stent implantation. In the USA this equates to some 125,000 cases per year. Conventional treatment for in-stent restenosis (balloon angioplasty and debulking) has been unsuccessful with 50-80% of cases suffering from further restenosis. Alternative treatment modalities were clearly required. Since radiotherapy had proven to be effective in treating the exuberant fibroelasticity of keloid scar formation and other non-malignant process such as ocular pterygia, it was assumed that this adjunctive therapy may also inhibit coronary restenosis. http://repub.eur.nl/res/pub/4825/ 2001-08-22T00:00:00Z Background Edge restenosis is a major problem after radioactive stenting. The cold-end stent has a radioactive mid-segment (15·9mm) and non-radioactive proximal and distal 5·7mm segments. Conceptually this may negate the impact of negative vascular remodelling at the edge of the radiation. Method and Results ECG-gated intravascular ultrasound with three-dimensional reconstruction was performed post-stent implantation and at the 6-month follow-up to assess restenosis within the margins of the stent and at the stent edges in 16 patients. Angiographic restenosis was witnessed in four patients, all in the proximal in-stent position. By intravascular ultrasound in-stent neointimal hyperplasia, with a >50% stented cross-sectional area, was seen in eight patients. This was witnessed proximally (n=2), distally (n=2) and in both segments (n=4). Echolucent tissue, dubbed the ‘black hole’ was seen as a significant component of neointimal hyperplasia in six out of the eight cases of restenosis. Neointimal hyperplasia was inhibited in the area of radiation: Δ neointimal hyperplasia=3·72mm3(8·6%); in-stent at the edges of radiation proximally and distally Δ neointimal hyperplasia was 7·9mm3(19·0%) and 11·4mm3(25·6%), respectively (P=0·017). At the stent edges there was no significant change in lumen volume. Conclusions Cold-end stenting results in increased neointimal hyperplasia in in-stent non-radioactive segments. http://repub.eur.nl/res/pub/12923/ 2001-07-19T00:00:00Z AIMS: This study is the contribution by the Thoraxcenter, Rotterdam, to the European(32)P Dose Response Trial, a non-randomized multicentre trial to evaluate the safety and efficacy of the radioactive Isostent in patients with single coronary artery disease. METHODS AND RESULTS: The radioactivity of the stent at implantation was 6--12 microCi. All patients received aspirin indefinitely and either ticlopidine or clopidogrel for 3 months. Quantitative coronary angiography measurements of both the stent area and the target lesion (stent area and up to 5 mm proximal and distal to the stent edges) were performed pre- and post-procedure and at the 5-month follow-up. Forty-two radioactive stents were implanted in 40 patients. Treated vessels were the left anterior descending coronary artery (n=20), right coronary artery (n=10) or left circumflex artery (n=10). Eight patients received additional non-radioactive stents. Lesion length measured 10+/-3 mm with a reference diameter of 3.07+/-0.69 mm. Minimal lumen diameter increased from 0.98+/-0.53 mm pre-procedure to 2.29+/-0.52 mm (target lesion) and 2.57+/-0.44 mm (stent area) post-procedure. There was one procedural non-Q wave myocardial infarction, due to transient thrombotic closure. Thirty-six patients returned for angiographical follow-up. Two patients had a total occlusion proximal to the radioactive stent. Of the patent vessels, none had in-stent restenosis. Edge restenosis was observed in 44%, occurring predominantly at the proximal edge. Target lesion revascularization was performed in 10 patients and target vessel revascularization in one patient. No additional clinical end-points occurred during follow-up. The minimal lumen diameter at follow-up averaged 1.66+/-0.71 mm (target lesion) and 2.12+/-0.72 (stent area); therefore late loss was 0.63+/-0.69 (target lesion) and 0.46+/-0.76 (stent area), resulting in a late loss index of 0.65+/-1.15 (target lesion) and 0.30+/-0.53 (stent area). CONCLUSION: These results indicate that the use of radioactive stents is safe and feasible, however, the high incidence of edge restenosis makes this technique currently clinically non-applicable. http://repub.eur.nl/res/pub/8301/ 2001-01-01T00:00:00Z OBJECTIVE: To study the relation between moderate coronary dissections, coronary flow velocity reserve (CFVR), and long term outcome. METHODS: 523 patients undergoing balloon angioplasty and sequential intracoronary Doppler measurements were examined as part of the DEBATE II trial (Doppler endpoints balloon angioplasty trial Europe). After successful balloon angioplasty, patients were randomised to stenting or no further treatment. Dissections were graded at the core laboratory by two observers and divided into four categories: none, mild (type A-B), moderate (type C), severe (types D to F). Patients with severe dissections (n = 128) or without available reference vessel CFVR (n = 139) were excluded. The remaining 256 patients were divided into two groups according to the presence (group A, n = 45) or absence (group B, n = 211) of moderate dissection. RESULTS: Following balloon angioplasty, there was no difference in CFVR between the two groups. At 12 months follow up, a higher rate of major adverse cardiac events was observed overall in group A than in group B (10 (22%) v 23 (11%), p = 0.041). However, the risk of major adverse events was similar in the subgroups receiving balloon angioplasty (group A, 6 (19%) v group B, 16 (16%), NS). Among group A patients, the adverse events risk was greater in those randomised to stenting (odds ratios 6.603 v 1.197, p = 0.046), whereas there was no difference in risk if the group was analysed according to whether the CFVR was < 2.5 or >/= 2.5 after balloon angioplasty. CONCLUSIONS: Moderate dissections left untreated result in no increased risk of major adverse cardiac events. Additional stenting does not improve the long term outcome. http://repub.eur.nl/res/pub/8349/ 2001-01-01T00:00:00Z OBJECTIVE: To assess the mechanism of restenosis after balloon angioplasty. DESIGN: Prospective study. PATIENTS: 13 patients treated with balloon angioplasty. INTERVENTIONS: 111 coronary subsegments (2 mm each) were analysed after balloon angioplasty and at a six month follow up using three dimensional intravascular ultrasound (IVUS). MAIN OUTCOME MEASURES: Qualitative and quantitative IVUS analysis. Total vessel (external elastic membrane), plaque, and lumen volume were measured in each 2 mm subsegment. Delta values were calculated (follow up - postprocedure). Remodelling was defined as any (positive or negative) change in total vessel volume. RESULTS: Positive remodelling was observed in 52 subsegments while negative remodelling occurred in 44. Remodelling, plaque type, and dissection were heterogeneously distributed along the coronary segments. Plaque composition was not associated with changes in IVUS indices, whereas dissected subsegments had a greater increase in total vessel volume than those without dissection (1.7 mm(3) v -0.33 mm(3), p = 0.04). Change in total vessel volume was correlated with changes in lumen (p < 0.05, r = 0.56) and plaque volumes (p < 0.05, r = 0.64). The site with maximum lumen loss was not the same site as the minimum lumen area at follow up in the majority (n = 10) of the vessels. In the multivariate model, residual plaque burden had an influence on negative remodelling (p = 0.001, 95% confidence interval (CI) -0.391 to -0.108), whereas dissection had an effect on total vessel increase (p = 0.002, 95% CI 1.168 to 4.969). CONCLUSIONS: The mechanism of lumen renarrowing after balloon angioplasty appears to be determined by unfavourable remodelling. However, different patterns of remodelling may occur in individual injured coronary segments, which highlights the complexity and influence of local factors in the restenotic process. http://repub.eur.nl/res/pub/9562/ 2001-01-01T00:00:00Z BACKGROUND: Restenosis after conventional stenting is almost exclusively caused by neointimal hyperplasia. Beta-particle-emitting radioactive stents decrease in-stent neointimal hyperplasia at 6-month follow-up. The purpose of this study was to evaluate the 1-year outcome of (32)P radioactive stents with an initial activity of 6 to 12 microCi using serial quantitative coronary angiography and volumetric ECG-gated 3D intravascular ultrasound (IVUS). METHODS AND RESULTS: Of 40 patients undergoing initial stent implantation, 26 were event-free after the 6-month follow-up period and 22 underwent repeat catheterization and IVUS at 1 year; they comprised half of the study population. Significant luminal deterioration was observed within the stents between 6 months and 1 year, as evidenced by a decrease in the angiographic minimum lumen diameter (-0.43+/-0.56 mm; P:=0.028) and in the mean lumen diameter in the stent (-0.55+/-0. 63 mm; P:=0.001); a significant increase in in-stent neointimal hyperplasia by IVUS (18.16+/-12.59 mm(3) at 6 months to 27.75+/-11. 99 mm(3) at 1 year; P:=0.001) was also observed. Target vessel revascularization was performed in 5 patients (23%). No patient experienced late occlusion, myocardial infarction, or death. By 1 year, 21 of the initial 40 patients (65%) remained event-free. CONCLUSIONS: Neointimal proliferation is delayed rather than prevented by radioactive stent implantation. Clinical outcome 1 year after the implantation of stents with an initial activity of 6 to 12 microCi is not favorable when compared with conventional stenting. http://repub.eur.nl/res/pub/12895/ 2000-12-01T00:00:00Z AIMS: We investigated the influence of tensile stress on plaque growth after balloon angioplasty with and without beta-radiation therapy. METHODS AND RESULTS: Thirty-one consecutive patients successfully treated with balloon angioplasty were analysed qualitatively and quantitatively by means of an ECG-gated three-dimensional intravascular ultrasound post-procedure and at follow-up. Eighteen patients were irradiated with catheter-based beta-radiation ((90)Sr/(90)Y source) and 13 were not (control). Studied segments were divided into 2 mm subsegments. Thus 184 irradiated and 111 non-irradiated subsegments were included. Tensile stress was calculated according to Laplace's law. The radiation dose was calculated by means of dose-volume histograms. Plaque growth was positively correlated to tensile stress in both the radiation and control groups (r=0.374, P=0.0001 and r=0.305, P=0.001). Low-dose subsegments (<6 Gy) had a significant correlation (r=0.410, P=0.0001) whereas no correlation was observed in the effective-dose subsegments (> or = 6 Gy). Multivariate analysis identified tensile stress as the only independent predictor of plaque increase in non-irradiated subsegments, whereas actual dose and plaque morphology were stronger predictors in irradiated subsegments. CONCLUSION: The results of this study suggest that plaque growth is related to tensile stress after balloon angioplasty. Intracoronary brachytherapy may alter the biophysical process on plaque growth when the prescribed dose is effectively delivered. http://repub.eur.nl/res/pub/4874/ 2000-08-15T00:00:00Z Limited data are available regarding the angiographic healing rate and physiologic impact of coronary artery dissections. Therefore, we studied the impact of coronary dissections on coronary flow velocity and outcome as well as their healing rate at 6-month follow-up balloon angioplasty. Of 297 patients who underwent balloon angioplasty, 225 underwent intracoronary Doppler measurements and 184 had Doppler and angiographic assessment at 6-month follow-up. Dissections were scored by an independent core lab (Cardialysis BV) and divided in 4 groups: mild (types A to B), moderate (type C), severe (D to F), and patients without dissections. Severe dissections (types D to F) were excluded from the analysis. Clinical, angiographic, and Doppler data were compared among the remaining 3 patient groups. From the 67 dissections detected after balloon angioplasty, only 3 (4.5%) remained unhealed at follow-up. Immediately after balloon angioplasty, the moderate dissection group was associated with a lower coronary flow velocity reserve than the patients with mild (2.16 +/- 0.60 vs 2.82 +/- 1.00, p = 0.037) or no dissections (2.16 +/- 0.60 vs 2.71 +/- 0.88, p = 0.046), respectively. In addition, higher recurrence of angina at 30 days was observed in the moderate group rather than in the mild group (5 [50%] vs 8 [16%], p = 0.0160) and in the patients without dissections (11 [12%], p = 0.007). After standard balloon angioplasty, the occurrence of unhealed dissections is a rare phenomenon. An impaired coronary flow reserve was observed after the development of nonocclusive type C dissections, which was associated with a worse short-term outcome. http://repub.eur.nl/res/pub/4905/ 2000-01-15T00:00:00Z Currently, several different designs of coronary stents are available. However, only a few of the new generation stents have been investigated in large randomized trials. Mechanical behavior of first-generation stents (Palmaz-Schatz, Gianturco-Roubin) may not be applied to the new designs. We investigated the chronic mechanical behavior (recoil) of 2 stents recently approved by the Food and Drug Administration (MULTILINK and NIR). Forty-eight patients with single-stent implantation (23 MULTILINK and 25 NIR) were assessed by means of volumetric 3-dimensional intravascular ultrasound analysis after the procedure and at 6-month follow-up. In addition, volumetric assessment of neointimal formation was performed. No significant chronic stent recoil was detected in both groups (Δ MULTILINK stent volume: +5.6 ± 41 mm3 [p = NS] and Δ NIR stent volume + 2.1 ± 26 mm3 [p = NS]). A similar degree of neointimal formation at 6 months was observed between the 2 stents (MULTILINK 46 ± 31.9 mm3 vs NIR 39.9 ± 27.6 mm3, p = NS). In conclusion, these 2 second-generation tubular stents did not show chronic recoil and appeared to promote similar proliferative response after implantation in human coronary arteries. http://repub.eur.nl/res/pub/4868/ 2000-01-01T00:00:00Z Background—Recent reports demonstrate that intracoronary radiation affects not only neointimal formation but also vascular remodeling. Radioactive stents and catheter-based techniques deliver radiation in different ways, suggesting that different patterns of remodeling after each technique may be expected. Methods and Results—We analyzed remodeling in 18 patients after conventional stent implantation, 16 patients after low-activity radioactive stent implantation, 16 patients after higher activity radioactive stent implantation, and, finally, 17 patients who underwent catheter-based radiation followed by conventional stent implantation. Intravascular ultrasound with 3D reconstruction was used after stent implantation and at the 6-month follow-up to assess remodeling within the stent margins and at its edges. Preprocedural characteristics were similar between groups. In-stent neointimal hyperplasia (NIH) was inhibited by high-activity radioactive stent implantation (NIH 9.0 mm3) and by catheter-based radiation followed by conventional stent implantation (NIH 6.9 mm3) compared with low-activity radioactive stent implantation (NIH 21.2 mm3) and conventional stent implantation (NIH 20.8 mm3) (P=0.008). No difference in plaque or total vessel volume was seen behind the stent in the conventional, low-activity, or high-activity stent implantation groups. However, significant increases in plaque behind the stent (15%) and in total vessel volume (8%) were seen in the group that underwent catheter-based radiation followed by conventional stent implantation. All 4 groups demonstrated significant late lumen loss at the stent edges; however, edge restenosis was seen only in the group subjected to high-activity stent implantation and appeared to be due to an increase in plaque and, to a lesser degree, to negative remodeling. Conclusions—Distinct differences in the patterns of remodeling exist between conventional, radioactive, and catheter-based radiotherapy with stenting. http://repub.eur.nl/res/pub/4888/ 2000-01-01T00:00:00Z Background—Inhomogeneity of dose distribution and anatomic aspects of the atherosclerotic plaque may influence the outcome of irradiated lesions after balloon angioplasty (BA). We evaluated the influence of delivered dose and morphological characteristics of coronary stenoses treated with ß-radiation after BA. Methods and Results—Eighteen consecutive patients treated according to the Beta Energy Restenosis Trial 1.5 were included in the study. The site of angioplasty was irradiated with the use of a ß-emitting 90Sr/90Y source. With the side branches used as anatomic landmarks, the irradiated area was identified and volumetric assessment was performed by 3D intracoronary ultrasound imaging after treatment and at 6 months. The type of tissue, the presence of dissection, and the vessel volumes were assessed every 2 mm within the irradiated area. The minimal dose absorbed by 90% of the adventitial volume (Dv90Adv) was calculated in each 2-mm segment. Diffuse calcified subsegments and those containing side branches were excluded. Two hundred six coronary subsegments were studied. Of those, 55 were defined as soft, 129 as hard, and 22 as normal/intimal thickening. Plaque volume showed less increase in hard segments as compared with soft and normal/intimal thickening segments (P<0.0001). Dv90Adv was associated with plaque volume at follow-up after a polynomial equation with linear and nonlinear components (r=0.71; P=0.0001). The multivariate regression analysis identified the independent predictors of the plaque volume at follow-up: plaque volume after treatment, Dv90Adv, and type of plaque. Conclusions—Residual plaque burden, delivered dose, and tissue composition play a fundamental role in the volumetric outcome at 6-month follow-up after ß-radiation therapy and BA. http://repub.eur.nl/res/pub/4889/ 2000-01-01T00:00:00Z Background—A recognized limitation of endovascular ß-radiation therapy is the development of new stenosis at the edges of the irradiated area. The combination of injury and low-dose radiation may be the precursor of this phenomenon. We translated the radio-oncological concept of "geographic miss" to define cases in which the radiation source did not fully cover the injured area. The aims of the study were to determine the incidence and causes of geographic miss and evaluate the impact of this inadequate treatment on the outcome of patients treated with intracoronary ß-radiation. Methods and Results—We analyzed 50 consecutive patients treated with ß-radiation after percutaneous coronary intervention. The prescribed dose ranged between 12 and 20 Gy at 2 mm from the source axis. By means of quantitative coronary angiography, the irradiated segment (IRS) and both edges were studied before and after intervention and at 6-month follow-up. Edges that were injured during the procedure constituted the geographic miss edges. Twenty-two edges were injured during the intervention, mainly because of procedural complications that extended the treatment beyond the margins of the IRS. Late loss was significantly higher in geographic miss edges than in IRSs and uninjured edges (0.84±0.6 versus 0.15±0.4 and 0.09±0.4 mm, respectively; P<0.0001). Similarly, restenosis rate was significantly higher in the injured edges (10% within IRS, 40.9% in geographic miss edges, and 1.9% in uninjured edges; P<0.001). Conclusions—These data support the hypothesis that the combination of injury and low-dose ß-radiation induces deleterious outcome. http://repub.eur.nl/res/pub/8353/ 2000-01-01T00:00:00Z OBJECTIVE: To evaluate the healing of balloon induced coronary artery dissection in individuals who have received beta radiation treatment and to propose a new intravascular ultrasound (IVUS) dissection score to facilitate the comparison of dissection through time. DESIGN: Retrospective study. SETTING: Tertiary referral centre. PATIENTS: 31 patients with stable angina pectoris, enrolled in the beta energy restenosis trial (BERT-1.5), were included. After excluding those who underwent stent implantation, the evaluable population was 22 patients. INTERVENTIONS: Balloon angioplasty and intracoronary radiation followed by quantitative coronary angiography (QCA) and IVUS. Repeat QCA and IVUS were performed at six month follow up. MAIN OUTCOME MEASURES: QCA and IVUS evidence of healing of dissection. Dissection classification for angiography was by the National Heart Lung Blood Institute scale. IVUS proven dissection was defined as partial or complete. The following IVUS defined characteristics of dissection were described in the affected coronary segments: length, depth, arc circumference, presence of flap, and dissection score. Dissection was defined as healed when all features of dissection had resolved. The calculated dose of radiation received by the dissected area in those with healed versus non-healed dissection was also compared. RESULTS: Angiography (type A = 5, B = 7, C = 4) and IVUS proven (partial = 12, complete = 4) dissections were seen in 16 patients following intervention. At six month follow up, six and eight unhealed dissections were seen by angiography (A = 2, B = 4) and IVUS (partial = 7, complete = 1), respectively. The mean IVUS dissection score was 5.2 (range 3-8) following the procedure, and 4.6 (range 3-7) at follow up. No correlation was found between the dose prescribed in the treated area and the presence of unhealed dissection. No change in anginal status was seen despite the presence of unhealed dissection. CONCLUSION: beta radiation appears to alter the normal healing process, resulting in unhealed dissection in certain individuals. In view of the delayed and abnormal healing observed, long term follow up is indicated given the possible late adverse effects of radiation. Although in this cohort no increase in cardiac events following coronary dissections was seen, larger populations are needed to confirm this phenomenon. Stenting of all coronary dissections may be warranted in patients scheduled for brachytherapy after balloon angioplasty. http://repub.eur.nl/res/pub/9223/ 2000-01-01T00:00:00Z http://repub.eur.nl/res/pub/9373/ 2000-01-01T00:00:00Z BACKGROUND: A recognized limitation of endovascular beta-radiation therapy is the development of new stenosis at the edges of the irradiated area. The combination of injury and low-dose radiation may be the precursor of this phenomenon. We translated the radio-oncological concept of "geographic miss" to define cases in which the radiation source did not fully cover the injured area. The aims of the study were to determine the incidence and causes of geographic miss and evaluate the impact of this inadequate treatment on the outcome of patients treated with intracoronary beta-radiation. METHODS AND RESULTS: We analyzed 50 consecutive patients treated with beta-radiation after percutaneous coronary intervention. The prescribed dose ranged between 12 and 20 Gy at 2 mm from the source axis. By means of quantitative coronary angiography, the irradiated segment (IRS) and both edges were studied before and after intervention and at 6-month follow-up. Edges that were injured during the procedure constituted the geographic miss edges. Twenty-two edges were injured during the intervention, mainly because of procedural complications that extended the treatment beyond the margins of the IRS. Late loss was significantly higher in geographic miss edges than in IRSs and uninjured edges (0.84+/-0.6 versus 0.15+/-0.4 and 0.09+/-0.4 mm, respectively; P<0.0001). Similarly, restenosis rate was significantly higher in the injured edges (10% within IRS, 40.9% in geographic miss edges, and 1.9% in uninjured edges; P<0.001). CONCLUSIONS: These data support the hypothesis that the combination of injury and low-dose beta-radiation induces deleterious outcome. http://repub.eur.nl/res/pub/9374/ 2000-01-01T00:00:00Z BACKGROUND: Inhomogeneity of dose distribution and anatomic aspects of the atherosclerotic plaque may influence the outcome of irradiated lesions after balloon angioplasty (BA). We evaluated the influence of delivered dose and morphological characteristics of coronary stenoses treated with beta-radiation after BA. METHODS AND RESULTS: Eighteen consecutive patients treated according to the Beta Energy Restenosis Trial 1.5 were included in the study. The site of angioplasty was irradiated with the use of a beta-emitting (90)Sr/(90)Y source. With the side branches used as anatomic landmarks, the irradiated area was identified and volumetric assessment was performed by 3D intracoronary ultrasound imaging after treatment and at 6 months. The type of tissue, the presence of dissection, and the vessel volumes were assessed every 2 mm within the irradiated area. The minimal dose absorbed by 90% of the adventitial volume (D(v90)Adv) was calculated in each 2-mm segment. Diffuse calcified subsegments and those containing side branches were excluded. Two hundred six coronary subsegments were studied. Of those, 55 were defined as soft, 129 as hard, and 22 as normal/intimal thickening. Plaque volume showed less increase in hard segments as compared with soft and normal/intimal thickening segments (P<0.0001). D(v90)Adv was associated with plaque volume at follow-up after a polynomial equation with linear and nonlinear components (r = 0.71; P = 0.0001). The multivariate regression analysis identified the independent predictors of the plaque volume at follow-up: plaque volume after treatment, D(v90)Adv, and type of plaque. CONCLUSIONS: Residual plaque burden, delivered dose, and tiss composition play a fundamental role in the volumetric outcome at 6-month follow-up after beta-radiation therapy and BA. http://repub.eur.nl/res/pub/9460/ 2000-01-01T00:00:00Z BACKGROUND: Recent reports demonstrate that intracoronary radiation affects not only neointimal formation but also vascular remodeling. Radioactive stents and catheter-based techniques deliver radiation in different ways, suggesting that different patterns of remodeling after each technique may be expected. METHODS AND RESULTS: We analyzed remodeling in 18 patients after conventional stent implantation, 16 patients after low-activity radioactive stent implantation, 16 patients after higher activity radioactive stent implantation, and, finally, 17 patients who underwent catheter-based radiation followed by conventional stent implantation. Intravascular ultrasound with 3D reconstruction was used after stent implantation and at the 6-month follow-up to assess remodeling within the stent margins and at its edges. Preprocedural characteristics were similar between groups. In-stent neointimal hyperplasia (NIH) was inhibited by high-activity radioactive stent implantation (NIH 9.0 mm(3)) and by catheter-based radiation followed by conventional stent implantation (NIH 6.9 mm(3)) compared with low-activity radioactive stent implantation (NIH 21.2 mm(3)) and conventional stent implantation (NIH 20.8 mm(3)) (P:=0.008). No difference in plaque or total vessel volume was seen behind the stent in the conventional, low-activity, or high-activity stent implantation groups. However, significant increases in plaque behind the stent (15%) and in total vessel volume (8%) were seen in the group that underwent catheter-based radiation followed by conventional stent implantation. All 4 groups demonstrated significant late lumen loss at the stent edges; however, edge restenosis was seen only in the group subjected to high-activity stent implantation and appeared to be due to an increase in plaque and, to a lesser degree, to negative remodeling. CONCLUSIONS: Distinct differences in the patterns of remodeling exist between conventional, radioactive, and catheter-based radiotherapy with stenting. http://repub.eur.nl/res/pub/9470/ 2000-01-01T00:00:00Z BACKGROUND: The "edge effect," late lumen loss at the margins of the treated segment, has become an important issue in the field of coronary brachytherapy. The aim of the present study was to assess the edge effect in noninjured margins adjacent to the irradiated segments after catheter-based intracoronary beta-irradiation. METHODS AND RESULTS: Fifty-three vessels were assessed by means of 3-dimensional intravascular ultrasound after the procedure and at 6- to 8-month follow-up. Fourteen vessels (placebo group) did not receive radiation (sham source), whereas 39 vessels were irradiated. In the irradiated group, 48 edges (5 mm in length) were identified as noninjured, whereas 18 noninjured edges were selected in the placebo group. We compared the volumetric intravascular ultrasound measurements of the noninjured edges of the irradiated vessels with the fully irradiated nonstented segments (IRS, n=27) (26-mm segments received the prescribed 100% isodose) and the noninjured edges of the vessels of the placebo patients. The lumen decreased (6 mm(3)) in the noninjured edges of the irradiated vessels at follow-up (P:=0. 001). We observed a similar increase in plaque volume in all segments: noninjured edges of the irradiated group (19.6%), noninjured edges of the placebo group (21.5%), and IRS (21.0%). The total vessel volume increased in the IRS in the 3 groups. No edge segment was subject to repeat revascularization. CONCLUSIONS: The edge effect occurs in the noninjured margins of radiation source train in both irradiated and placebo patients. Thus, low-dose radiation may not play an important role in this phenomenon, whereas nonmeasurable device injury may be considered a plausible alternative explanation. http://repub.eur.nl/res/pub/9100/ 1999-06-02T00:00:00Z http://repub.eur.nl/res/pub/4931/ 1999-01-01T00:00:00Z Cardiogenic shock secondary to acute myocardial infarction results in the death of most affected indi- viduals. This grim reality persists in spite of vigorous attempts at providing inotropic support using phar- macological agents, thrombolytic regimes and intra- aortic balloon pumping. http://repub.eur.nl/res/pub/9132/ 1999-01-01T00:00:00Z http://repub.eur.nl/res/pub/9154/ 1999-01-01T00:00:00Z BACKGROUND: Intracoronary brachytherapy appears to be a promising technology to prevent restenosis. Presently, limited data are available regarding the late safety of this therapeutic modality. The aim of the study was to determine the incidence of late (>1 month) thrombosis after PTCA and radiotherapy. METHODS AND RESULTS: From April 1997 to March 1999, we successfully treated 108 patients with PTCA followed by intracoronary beta-radiation. Ninety-one patients have completed at least 2 months of clinical follow-up. Of these patients, 6.6% (6 patients) presented with sudden thrombotic events confirmed by angiography 2 to 15 months after intervention (2 balloon angioplasty and 4 stent). Some factors (overlapping stents, unhealed dissection) may have triggered the thrombosis process, but the timing of the event is extremely unusual. Therefore, the effect of radiation on delaying the healing process and maintaining a thrombogenic coronary surface is proposed as the most plausible mechanism to explain such late events. CONCLUSIONS: Late and sudden thrombosis after PTCA followed by intracoronary radiotherapy is a new phenomenon in interventional cardiology. http://repub.eur.nl/res/pub/9161/ 1999-01-01T00:00:00Z BACKGROUND: Endovascular radiation appears to inhibit intimal thickening after overstretching balloon injury in animal models. The effect of brachytherapy on vascular remodeling is unknown. The aim of the study was to determine the evolution of coronary vessel dimensions after intracoronary irradiation after successful balloon angioplasty in humans. METHODS AND RESULTS: Twenty-one consecutive patients treated with balloon angioplasty and beta-radiation according to the Beta Energy Restenosis Trial-1.5 were included in the study. Volumetric assessment of the irradiated segment and both edges was performed after brachytherapy and at 6-month follow-up. Intravascular ultrasound images were acquired by means of ECG-triggered pullback, and 3-D reconstruction was performed by automated edge detection, allowing the calculation of lumen, plaque, and external elastic membrane (EEM) volumes. In the irradiated segments, mean EEM and plaque volumes increased significantly (451+/-128 to 490.9+/-159 mm(3) and 201.2+/-59 to 241.7+/-74 mm(3); P=0.01 and P=0.001, respectively), whereas luminal volume remained unchanged (250.8+/-91 to 249.2+/-102 mm(3); P=NS). The edges demonstrated an increase in mean plaque volume (26.8+/-12 to 32. 6+/-10 mm(3), P=0.0001) and no net change in mean EEM volume (71. 4+/-24 to 70.9+/-24 mm(3), P=NS), resulting in a decrease in mean luminal volume (44.6+/-16 to 38.3+/-16 mm(3), P=0.01). CONCLUSIONS: A different pattern of remodeling is observed in coronary segments treated with beta-radiation after successful balloon angioplasty. In the irradiated segments, the adaptive increase of EEM volume appears to be the major contributor to the luminal volume at follow-up. Conversely, both edges showed an increase in plaque volume without a net change in EEM volume. http://repub.eur.nl/res/pub/9177/ 1999-01-01T00:00:00Z BACKGROUND: Abnormal endothelium-dependent coronary vasomotion has been reported after balloon angioplasty (BA), as well as after intracoronary radiation. However, the long-term effect on coronary vasomotion is not known. The aim of this study was to evaluate the long-term vasomotion of coronary segments treated with BA and brachytherapy. METHODS AND RESULTS: Patients with single de novo lesions treated either with BA followed by intracoronary beta-irradiation (according to the Beta Energy Restenosis Trial-1.5) or with BA alone were eligible. Of these groups, those patients in stable condition who returned for 6-month angiographic follow-up formed the study population (n=19, irradiated group and n=11, control group). Endothelium-dependent coronary vasomotion was assessed by selective infusion of serial doses of acetylcholine (ACh) proximally to the treated area. Mean luminal diameter was calculated by quantitative coronary angiography both in the treated area and in distal segments. Endothelial dysfunction was defined as a vasoconstriction after the maximal dose of ACh (10(-6) mol/L). Seventeen irradiated segments (89.5%) demonstrated normal endothelial function. In contrast, 10 distal nonirradiated segments (53%) and 5 control segments (45%) demonstrated endothelium-dependent vasoconstriction (-19+/-17% and -9.0+/-5%, respectively). Mean percentage of change in mean luminal diameter after ACh was significantly higher in irradiated segments (P=0.01). CONCLUSIONS: Endothelium-dependent vasomotion of coronary segments treated with BA followed by beta-radiation is restored in the majority of stable patients at 6-month follow-up. This functional response appeared to be better than those documented both in the distal segments and in segments treated with BA alone. http://repub.eur.nl/res/pub/9179/ 1999-01-01T00:00:00Z BACKGROUND: This study represents the Heart Center Rotterdam's contribution to the Isostents for Restenosis Intervention Study, a nonrandomized multicenter trial evaluating the safety and feasibility of the radioactive Isostent in patients with single coronary artery disease. Restenosis after stent implantation is primarily caused by neointimal hyperplasia. In animal studies, beta-particle-emitting radioactive stents decrease neointimal hyperplasia by inhibiting smooth muscle cell proliferation. METHODS AND RESULTS: The radioisotope (32)P, a beta-particle emitter with a half-life of 14.3 days, was directly embedded into the Isostent. The calculated range of radioactivity was 0.75 to 1.5 microCi. Quantitative coronary angiography measurements were performed before and after the procedure and at 6-month follow-up. A total of 31 radioactive stents were used in 26 patients; 30 (97%) were successfully implanted, and 1 was embolized. Treated lesions were in the left anterior descending coronary artery (n=12), the right coronary artery (n=8), or the left circumflex coronary artery (n=6). Five patients received additional, nonradioactive stents. Treated lesion lengths were 13+/-4 mm, with a reference diameter of 2.93+/-0. 47 mm. Minimum lumen diameter increased from 0.87+/-0.28 mm preprocedure to 2.84+/-0.35 mm postprocedure. No in-hospital adverse cardiac events occurred. All patients received aspirin indefinitely and ticlopidine for 4 weeks. Twenty-three patients (88%) returned for 6-month angiographic follow-up; 17% of them had in-stent restenosis, and 13% had repeat revascularization. No restenosis was observed at the stent edges. Minimum lumen diameter at follow-up averaged 1.85+/-0.69 mm, which resulted in a late loss of 0.99+/-0. 59 mm and a late loss index of 0.53+/-0.35. No other major cardiac events occurred during the 6-month follow-up. CONCLUSIONS: The use of radioactive stents with an activity of 0.75 to 1.5 microCi is safe and feasible. http://repub.eur.nl/res/pub/9185/ 1999-01-01T00:00:00Z BACKGROUND: Intravascular ultrasound (IVUS)-guided stent implantation and the availability of a reference chart to predict the expected in-stent restenosis rate based on operator-dependent IVUS parameters may interactively facilitate optimal stent placement. The use of IVUS guidance protects against undue risks of dissection or rupture. METHODS AND RESULTS: IVUS-determined post-stent-implantation predictors of 6-month in-stent restenosis on quantitative coronary angiography (QCA) were identified by logistic regression analysis. These predictors were used to construct a reference chart that predicts the expected 6-month QCA restenosis rate. IVUS and QCA data were obtained from 3 registries (MUSIC [Multicenter Ultrasound Stenting in Coronaries study], WEST-II [West European Stent Trial II], and ESSEX [European Scimed Stent EXperience]) and 2 randomized in-stent restenosis trials (ERASER [Evaluation of ReoPro And Stenting to Eliminate Restenosis] and TRAPIST [TRApidil vs placebo to Prevent In-STent intimal hyperplasia]). In-stent restenosis was defined as luminal diameter stenosis >50% by QCA. IVUS predictors were minimum and mean in-stent area, stent length, and in-stent diameter. Multiple models were constructed with multivariate logistic regression analysis. The model containing minimum in-stent area and stent length best fit the Hosmer-Lemeshow goodness-of-fit test. This model was used to construct a reference chart to calculate the expected 6-month restenosis rate. CONCLUSIONS: The expected 6-month in-stent restenosis rate after stent implantation for short lesions in relatively large vessels can be predicted by use of in-stent minimal area (which is inversely related to restenosis) and stent length (which is directly related to restenosis), both of which can be read from a simple reference chart.